Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

Abstract

Background/Aims: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. Methods: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I² were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF^V600E mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. Results: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF^V600E mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF^V600E mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF^V600E mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). Conclusion: This meta-analysis confirmed significant associations between BRAF^V600E mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF^V600Emutation for PTC prognosis.

CHK2 Promotes Anoikis and is Associated with the Progression of Papillary Thyroid Cancer

“…Compared with those who have fewer than five metastatic lymph nodes (LN mets), patients with five or more LN mets have a higher risk of recurrence [12]. Other factors are also associated with an unfavorable prognosis including age (>45 years), male sex, histology (tall cell variant histology), extrathyroidal extension (EXE), larger tumor size, stage III and IV disease, resistance to radioiodine therapy, distant metastasis, positive family history, and the BRAF V600E mutation [6, 7, 9, 13-19]. Therefore, the underlying inherent molecular mechanism of the aggressiveness and progression of PTC has great significance in the ability to understand the biological basis for the improvement in clinical outcomes [20-22].…”

The synergic effect of BRAF^V600E mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

“…Based on these study reports, the PTC that coexists with BRAF V600E mutation is more likely to have multifocality [18]. Nonetheless, most of those studies only explored the relationship between BRAF V600E mutation and multifocality, and the studies focused on the combined interaction of BRAF V600E mutation and multifocality on CLNM in PTC are still rare.…”

The mTOR Kinase Inhibitor CZ415 Inhibits Human Papillary Thyroid Carcinoma Cell Growth

“…Its incidence has been tripled in the past decades [3-5]. Over three-quarter of thyroid cancers are papillary thyroid carcinomas (PTC) [1, 2].…”